There is substantial evidence that changes in memory function occur during healthy aging. Recent findings with aged rats suggest that aging is associated with impairment in pattern separation or the process of creating different representations from similar inputs. Additional evidence also suggests that this impairment may be linked to hyperactivity in CA3 hippocampal neurons. Functional MRI has been used extensively to study memory changes with aging, but due to the method's coarse resolution, studying activation at the level of hippocampal subfields in a manner similar to the animal studies has posed quite a challenge. However, recent technological advances have allowed us to overcome this limitation giving us the potential to assess subtle changes in function and corresponding changes in neural computations. The aim of the current proposal is to study these changes using high-resolution (1.5 mm) fMRI coupled with sophisticated alignment techniques that respect individuals' anatomy at the level of hippocampal subfields, and tasks designed to test computations specific to hippocampal subfields. We propose to test young healthy and aged healthy individuals using two tasks: a continuous paired-associate learning task and a incidental encoding task, both of which manipulate demand on pattern separation in different ways. We hypothesize that as pattern separation demands increase, behavioral and neural differences between groups will be more pronounced, and that the earliest neural changes will be detected in the CA3 region. If successful, this study will provide a clear picture of the exact locus and nature of the changes in memory computations with healthy aging. This will help us make the critical link between animal and human studies, enhance our understanding of aging as the primary risk factor for dementia, and pave the way to identifying pre-clinical markers and developing therapies to decelerate progression to dementia. PUBLIC HEALTH RELEVANCE: The proposed research examines detailed aspects about the neural bases of age-related memory decline (the most common cognitive complaint associated with aging). If successful, this study will provide a clear picture of the exact locus and nature of the changes in memory computations with healthy aging. This will help us make the critical link between animal and human studies, enhance our understanding of aging as the primary risk factor for dementia, and pave the way to identifying pre-clinical markers for disorders such as Mild Cognitive Impairment and Alzheimer's disease. [unreadable] [unreadable] [unreadable]